title: A robust approach to enhance tumor-selective accumulation of nanoparticles.
abstract: While nanoparticles have shown great promise as drug carriers in cancer therapy, their effectiveness is critically dependent on the structural characteristics of the tumor vasculature. Here we demonstrate that several agents capable of inducing vascular responses akin to those observed in inflammatory processes enhance the accumulation of nanoparticles in tumors. The vascular-active agents tested in this study included a bacterium, a pro-inflammatory cytokine, and microtubule-destabilizing drugs. Using radiolabeled nanoparticles, we show that such agents can increase the tumor to blood ratio of radioactivity by more than 20-fold compared to nanoparticles alone. Moreover, vascular-active agents dramatically improved the therapeutic effect of nanoparticles containing radioactive isotopes or chemotherapeutic agents. This resulted in cures of animals with subcutaneous tumors and significantly prolonged the survival of animals with orthotopic brain tumors. In principle, a variety of vascular-active agents and macromolecular anticancer formulations can be combined, which makes this approach broadly applicable and particularly suited for the treatment of patients who have failed standard therapies.
authors.affiliation: The Ludwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute and Sidney Kimmel Cancer Center at the Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Qiao
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Sridhar
authors.initials: S
authors.lastname: Nimmagadda
authors.forename: Renyuan
authors.initials: R
authors.lastname: Bai
authors.forename: Verena
authors.initials: V
authors.lastname: Staedtke
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Foss
authors.forename: Ian
authors.initials: I
authors.lastname: Cheong
authors.forename: Matthias
authors.initials: M
authors.lastname: Holdhoff
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kato
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Riggins
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: Luis A
authors.initials: LA
authors.lastname: Diaz
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.forename: Shibin
authors.initials: S
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers